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By Hilary E. Beggs, Dorreyah Schahin-reed, Keling Zang, Ra Goebbels, Klaus-armin Nave, Jessica Gorski, Kevin R. Jones, David Sretavan and Louis F. Reichardt


Targeted deletion of focal adhesion kinase (fak) in the developing dorsal forebrain resulted in local disruptions of the cortical basement membrane located be-tween the neuroepithelium and pia-meninges. At disruption sites, clusters of neurons invaded the marginal zone. Retraction of radial glial endfeet, midline fusion of brain hemispheres, and gliosis also occurred, simi-lar to type II cobblestone lissencephaly as seen in congenital muscular dystrophy. Interestingly, targeted deletion of fak in neurons alone did not result in corti-cal ectopias, indicating that fak deletion from glia is required for neuronal mislocalization. Unexpectedly, fak deletion specifically from meningeal fibroblasts elicited similar cortical ectopias in vivo and altered laminin organization in vitro. These observations pro-vide compelling evidence that FAK plays a key signaling role in cortical basement membrane assembly and/ or remodeling. In addition, FAK is required within neurons during development because neuron-specific fak deletion alters dendritic morphology in the absence of lamination defects

Year: 2013
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